Weisenberger, Jill - FINAL€¦ · ñ l í õ l î ì î ì ó 7'9luwxdo6\psrvlxp /lyhu ,qvxolq...

$: Weisenberger, Jill - FINAL€¦ · ñ l í õ l î ì î ì ó 7'9luwxdo6\psrvlxp /lyhu ,qvxolq 5hvlvwdqfh (iihfwv srvw sudqgldo joxfrvh ,qvxolq ohyhov duh kljk diwhu hdwlqj exw wkh$
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P R E S E N T E RP R E S E N T E R

Prediabetes is NOT Pre-ProblemThe Path of Metabolic Dysregulation

Jill Weisenberger, MS, RDN, CDE, CHWC, FAND

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Learning Objectives1. Describe the disease process from normal blood glucose levels to

those in the prediabetes range to the diabetes range and to the stage in which exogenous insulin is required.

2. Identify at least 4 common metabolic abnormalities among people with prediabetes.

3. Identify at least 5 foods that are linked to less insulin resistance and/or the incidence of type 2 diabetes.

4. List and describe at least 5 lifestyle habits that can impact the progression/reversal of prediabetes.

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Disclosures• Norwegian Seafood Council

• Corteva

• Pyure Organic Stevia

• Calorie Control Council

• 4 books+ by American Diabetes Association

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Scary Numbers • 1 in 3 adults

• 88 million

• 15% diagnosed• 85% undiagnosed

• Diabetes• 10.5% population• 34.2 million people

https://www.cdc.gov/diabetes/pdfs/data/statistics/national-diabetes-statistics-report.pdf

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Prediabetes Treatment• Weight loss

• 7% body weight

• Physical activity• > 150 minutes weekly

• Diet• Avoid sugary drinks

• Medication• Metformin

• Tobacco cessation

Diabetes Care 2019;42:731–754

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Maria• 58 years old, upper middle class, well-

educated

• Significant family h/o type 2

• BMI: 19

• A1C: 6.2%

• Power walker: 60 – 90 minutes daily

• “Eats clean” & all day• Almonds, almond milk, oats, flaxseed,

salad, fruit including under-ripe bananas, avocados, crab cakes, sweet potatoes, tofu, lentils, yogurt, pretzels, red wine

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Pathogenesis

Insulin resistance normal blood glucose

Prediabetes Diabetes Diabetes requiring insulin

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Diabetes Prevention Program (DPP)

• 3,234 high-risk people, average 3 years

• Intensive Lifestyle• Goal: 7% loss of BW, 150 min physical activity weekly

• Standard Care• General diet & exercise advice

• Metformin• General diet & exercise advice + metformin BID

https://dppos.bsc.gwu.edu/web/dppos/dppos

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Diabetes Prevention Outcomes Study

tk Intensive Lifestyle

(%)

Metformin(%) NOTES

DPP 3-year study 58 31

DPPOS 10 year data 34 18 Less CVD meds with

Lifestyle

DPPOS 15 year data 27 17 B12 deficiency noted

https://dppos.bsc.gwu.edu/web/dppos/dppos

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DPP Strategies

Self-monitor weight

Track physical activity

Record food intake

Decrease calories

Choose wholesome foods

Manage stress

Maintain motivation

Mindset: stop harmful negative thinking

https://www.cdc.gov/diabetes/prevention/lifestyle-program/t2/t2materials.html

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Other Prevention StudiesIntensive Lifestyle

(%) Notes

Da Qing39

Diet: ↑ veg, ↓ alcohol & sugarResults: ↓ all-cause & CVD mortality & microvascular complications

Finnish DPS 13 year 38

Diet: ↑ fiber CHO, ↓ SFAResults:↑ fat, ↓CHO = ↑ DM

DPPOS 10 year 34 Results: ↓ CVD meds

DPPOS 15 year 27Results: metformin for GDM, starting ↑FBG & A1C

ADA Standards of Medical Care in Diabetes-2020

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Weight Loss Drug Helps Prevent

Type 2 Diabetes

3 Years of Liraglutide vs Placebo

• 1128 participants completed the study

• 3.0 mg liraglutide (Saxenda)

• ↓ calorie, ↑activity, phone & web-based

• Average weight loss: 6%

• Reduced progression to DM: 66%• Completers only: 80% risk reduction

Carel W le Roux et al. SC Lancet. 2017 Apr 8;389(10077

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Diagnostic Criteria

Measurement Prediabetes Diabetes

Fasting Plasma Glucose > 100 – 125 mg/dl > 126 mg/dl

2-hour OGTT > 140 – 199 mg/dl > 200 mg/dl

Random Plasma Glucose (+ symptoms) ---- > 200 mg/dl

A1C 5.7 – 6.4 % > 6.5%


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ADA Prevention or Delay of Type 2 Diabetes

• Screen at least annually

• Increased vigilance for CV risk factors

• Refer to DPP or similar program

• Consider metformin, especially for

• BMI > 35

• H/o GDM

• < 60 years


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Prediabetes

Type 2 diabetes

Heart disease

Stroke

CDC Infographic

https://www.cdc.gov/diabetes/library/socialMedia/infographics.html

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Traditional View of Type 2 Diabetes: The Triumverate

Hyperglycemia

Increased Liver Output

Decreased Muscle Uptake

Impaired Insulin Secretion

DeFronzo. Diabetes. 2009; 58(4): 773-795

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Muscle Insulin ResistanceImpaired glucose uptake after eating

• By at least 50%• Post-prandial hyperglycemia

Exercise (muscle contraction): induced glucose uptake is independent of insulin


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Muscle Insulin Resistance

The muscle resists the action of insulin, so it’s slow to allow glucose into the cells. But the

muscles welcome glucose during exercise, no matter

what.

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Liver Insulin ResistanceEffects post-prandial glucose

• Insulin levels are high after eating, but the liver ignores insulin and sends out more glucose

Effects FBG

• Excess hepatic gluconeogenesis, unrelated to food


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Liver Insulin Resistance

The liver’s job is to send out glucose during the night. But with insulin

resistance, it dumps out too much. And this is NOT related to what you

ate last night.

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Decreased β-cell Function• Relative insulin insufficiency

• Fail over time, leading first to high post-prandial BG levels, then to high FBG

• Progressive loss of beta-cell function that determines the rate of disease progression


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Decreased β-cell Function

Your pancreas makes extra insulin to compensate for your cells refusing to

use it properly. It used to make enough to keep BG in the normal

range. Now your pancreas can’t make enough insulin. Blame your pancreas!

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Pathogenesis

Insulin resistance normal blood glucose

Prediabetes Diabetes Diabetes requiring insulin

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Cardiovascular Complications

Microvascular Complications

Onset of Type 2 DM

Type 2 DMPre DM

Ramlo-Halsted. Primary Care: 1999 26(4)

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The Ominous Octet

Hyperglycemia

Increased Liver Output

Decreased Muscle Uptake

Impaired Insulin Secretion

Decreased Incretin EffectStream of FFA Increased Glucagon Secretion

Increased Glucose Reabsorption

Increased Appetite


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Fat Insulin Resistance

FFA flood the bloodstream

Muscle IR Impaired β-cellsLiver IR

Normal insulin action to inhibit TG breakdown is faulty

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Muscle Uptake

Insulin Secretion

Liver Output


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𝜶-Cells of the Pancreas• Secrete glucagon, counter-regulatory to

insulin• Excess in type 2 diabetes, likely in prediabetes

• High fasting glucagon levels correlate with high rate of liver glucose production, leading to high FBG

• In type 2 DM, insulin fails to suppress glucagon after eating, leading to high postprandial BG


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𝜶-Cells of the Pancreas

Your liver is leaky and letting out too

much glucose.

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Role of Incretin HormonesGLP-1 And GIP

• Released after eating

• Important for insulin release

Normal Role of GLP-1

• β-cells: Enhances glucose-dependent insulin secretion• Brain: Promotes satiety, reduces appetite

• α-cells: Reduces glucagon secretion after eating

• Liver: Reduces hepatic glucose output (via less glucagon)

DeFronzo. Diabetes. 2009; 58(4): 773-795AADE Desk -3rd-edition American Association of Diabetes Educators

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Normal Role of GLP-1

Hormones in your gut act nutty, causing you to have higher blood glucose levels

and even make you hungrier.

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Insulin Resistance of the BrainNeurotransmitter dysregulation

• Brain neurotransmitters affect appetite and food intake

• GLP-1 resistance in the brain increases food intake, leading to weight dysregulation• Muscle insulin resistance• Liver insulin resistance• β-cell failure


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Insulin Resistance of the Brain

Problems with your hormones and chemical messengers in your brain

can make it harder to regulate your appetite.

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Increased Reabsorption in the Kidneys• Renal threshold: ~ 180 mg/dl

• Higher in people with type 2 diabetes• Contributes to the maintenance of

hyperglycemia• More likely in type 2 diabetes than in

prediabetes


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Instead of letting you pee out excess blood sugar, your kidneys

send it back into your blood…

DIABETES ONLY

Increased Reabsorption in the Kidneys

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Pathophysiology Summary• Many years from early IR to prediabetes to type

2 diabetes to complete loss of insulin producing ability

• Prediabetes is multifactorial and affects liver, muscle, fat, pancreas, brain, GI tract

• Underlying cause is IR, thus treatment must include insulin-sensitizing behaviors + in later-stages usually insulin-sensitizing meds

• Consider ALL of insulin’s roles

3636

Abnormal Lipid Metabolism

LDL ApoB HDL TG

Cardiometabolic RiskGlobal Diabetes / CVD Risk

Overweight / Obesity

Inflammation Hypercoagulation

Hypertension

SmokingPhysical InactivityUnhealthy Eating

Age, Race, Gender,

Family History

GlucoseBP Lipids

Age Genetics

Insulin ResistanceInsulin Resistance

Syndrome

American Diabetes Association. (2015). Cardiometabolic Risk,Type 2 Diabetes and Cardiovascular Disease. https://professional.diabetes.org/sites/professional.diabetes.org/files/media/cardiometabolicrisk2015.pdf

Cardiometabolic Risk

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Markers of Insulin Resistance

TG: HDL (mg/dl)

Higher value = IR and CVD risk1

Some experts use 32

TG 281

HDL 31

LDL 128

1. Diabetes Care 2000; 23(3) 1679-1685 2. McLaughlin et al. 2003; 139(10): 802-809

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Diabetes-Cancer Link: Expected Higher in Prediabetes

Prediabetes and diabetes are also associated with

increased death from cancer, even when BMI and

other factors are considered.

Cancer Site Risk RatioLiver 2.01Pancreas 1.94Endometrium 2.10

Biliary Tract 1.43Colorectum 1.27Kidney 1.42Bladder 1.24Breast 1.20

Shikata et al. Cancer Sci 2013; 104: 9-14

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Maria• 58 years old, upper middle class, well-

educated

• Significant family h/o type 2

• BMI: 19

• A1C: 6.2%

• Power walker: 60-90 minutes daily

• “Eats clean” and all day

A1C 5.5% 2 months later (6.2%)

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Diet

Higher intakes of nuts, berries, yogurt, coffee, and tea are associated with reduced diabetes risk. Conversely, red meats and sugar-sweetened beverages are associated with an increased risk.

2018 ADA Standards of Care

An emphasis on whole grains, legumes, nuts, fruits and vegetables, and minimal refined and processed foods is important.

2020 ADA Standards of Care

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Dietary Pattern: Mediterranean

23% less likely to develop diabetesMeta-analysis from around the world:

52% less likely after 4 yearsPREDIMED:

• Seafood, fruits, vegetables, whole grains, olive oil, nuts, other plants

• Wine with meals and fruit for dessertFood choices

Diabetes Spectr. 2017;(2):72-76.

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Dietary Pattern: Vegan/Vegetarian

• Vegan diets outperformed vegetarian• All vegetarian diets outperformed

nonvegetarian diet

Adventist Health Study 2

• More fiber, phytochemicals• Less heme ironMechanisms

Diabetes Care. 2009; 32:791-796

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Dietary Pattern: DASH

• 20% reduced riskMeta-analysis1

• Improved fasting insulin, FBG, insulin actionPREMIER Study2

• Lower in fat and higher in animal products compared to Mediterranean

Fruits, vegetables, poultry, fish, nuts, whole grains, nonfat

and low-fat dairy

Diabetes Spectr. 2017;(2):76-81Diabetes Care 2004;27(2):40-347

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Diet

Higher intakes of nuts, berries, yogurt, coffee, and tea are associated with reduced diabetes risk.

2018 ADA Standards of

Care

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Pulses and Other LegumesFBG (long and short term)

• Magnesium

• Phytonutrients

• Fibers

• Resistant starches

Diabetologia. 2009;52(8):1479-1495

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BerriesPopulation study-middle aged adults (Finland)

• 35% reduced risk with greatest berry consumption

• Polyphenols

• Fibers

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Am J Clin Nutr. 2014:99(2):328-333

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NutsStudies show mixed results on diabetes prevention

• Fiber

• Magnesium

• Phytonutrients

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YogurtHealth Professionals Follow-Up Study, Nurses’ Health Study, and Nurses’ Health Study II

• Increased 1 serving daily associated with 18% reduced risk

• Probiotics

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BMC Medicine. 2014;12:215

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Coffee and Tea

Ris

k of

Dia

bete

s

Daily Cups

33% risk with 6 cups vs. 0

Regular & decafChlorogenic acidOther bioactives

Coffee1

15% risk with > 4 cups vs. 0

Regular & decafCatechinsOther bioactives

Tea2

Diabetes Care Feb 2014, 37 (2) 569-586Br J Nutr. 2014;111(8):1329-1339

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Oats and BarleyBeta-glucan

• Viscous fiber• Improves insulin action,

lowers blood glucose• Lowers cholesterol levels

• Uncooked oats• Resistant starch

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J Am Coll Nutr. 2005;24(3)182-188

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Alcohol

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Physical Activity RecommendationsCardiovascular Exercise

• 3 x weekly, no more than 2 consecutive days without

• > 150 min weekly

Strength Training

• 2-3 sessions on non-consecutive days

Reduce Sedentary Time

• Interrupt prolonged sitting with 3-min breaks every 30 min

Diabetes Care 2016 Nov; 39(11)

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Cardiovascular ExerciseReduces insulin resistance for 2-48 hours

• Best daily• 20-minute walk after meals

Non-insulin mediated glucose uptake


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Strength Training• Reduces insulin resistance as well

as CV exercise• Effects are additive

• Non-insulin mediated glucose uptake

• Repository for PP BG


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Reduce Sedentary Behavior

Sedentary Behavior:

TV, gaming, driving, etc

Muscle contraction, glucose uptake, venous sufficiency, EE, LPL function, HDL cholesterol

Incr

easi

ng

Decreases


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Inactivity Tracker

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SleepInadequate Sleep1

• Linked to weight gain, obesity, diabetes, CVD

• More ghrelin, less leptin

• Decreased insulin resistance• Even short term (1 bad night)

U-shaped curve: lowest risk 7-8 hours2

JCEM. 2010;95(6):2963-2968Diabetes Care. 2015;38(3):529-537

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Conclusion: Overall Healthy LifestyleEating patterns: more whole foods• Low carb not requiredPhysical activity

• Cardio, strength, reduced sedentary behavior

SleepSmoking cessationWeight loss

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Questions?Jill Weisenberger, MS, RDN, CDE, CHWC, FAND

Jillweisenberger.com

NutritionJill

NutritionJill

[email protected]

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Weisenberger, Jill - FINAL€¦ · ñ l í õ l î ì î ì ó 7'9luwxdo6\psrvlxp /lyhu ,qvxolq...

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